Prp19: Difference between revisions

{{STRUCTURE_3lrv |  PDB=3lrv  | SCENE= }}

PRP19 (precusor RNA processing 19) is a splicing factor which is essential for proper pre-mRNA processing.<ref>PMID:10092627</ref>Its presence is required prior to the first splicing step, in which the 5' splice site is cleaved and a lariat intron/3' exon intermediate is formed. Through various isolation methods, over 40 PRP genes have been identified<ref name = "functional">PMID:8194532</ref> - many of which have very similar homology and motifs such as [http://en.wikipedia.org/wiki/Zinc_fingers <i>Zinc fingers</i>], RNA binding motifs, ATP dependent helicase and a motif for the beta subunit of G protein.<ref name="novel">PMID:8441419</ref> However, PRP19 had no homological similarities to any known sequences. The function of PRP proteins can be broken down into three main categories, those involved in the first chemical step, such as PRP19, those involved in the accumulation of splicing intermediates, and those involved in the formation of the lariat-intron product.   

U-Box proteins are a class of ubiquitin ligases whose structures are generally stabilized by hydrogen bonds and or salt bridges.<ref>pmid:11274149.</ref> In mammals, these proteins have been found to associate and interact with molecular chaperons such as HSP90 and HSP70, providing evidence that they may be involved in the degradation of mis-folded proteins.<ref>http://smart.embl-heidelberg.de/smart/do_annotation.pl?ACC=SM00504</ref> PRP19's U-Box domain is located at the beginning of its amino acid sequence and is comprised of 61 residues. The U-Box domain's structure was first solved by NMR in 2003<Ref>pmid:12627222</ref> and by X-ray crystallography in 2006<ref name="something"/>. The protein was purified from yeast (''S. cerevisiae'') and the resulting crystal structure was solved via X-Ray diffraction at a resolution of 1.5 Angstroms and revealed that the U-Box fragment consisted of six chains.

The NTC consists of at least 8 protein components and is associated with the spliceosome as U4 dissociates or immediately there after. Research has shown that the PRP19 associated complex is required for a reaction in which the structure of the U6 snRNP is re-arranged, involving destabilization of [http://en.wikipedia.org/wiki/LSm<i>Lsm</i>] proteins. This destabilization is thought to help facilitate interaction between the intron closest to the 5’ splice site and the Lsm binding site of U6.<ref>PMID:16540691</ref> The NTC may also function to increase specificity between the U5 snRNP and the 5' splice site. Additionally, it may play a role in the specificity of the base pairing between U5 and U6. Currently it is uncertain whether base pairing between U2 and U6 requires participation of the NTC complex.<ref>pmid:15994330</ref>